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The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b
Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 b...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325102/ https://www.ncbi.nlm.nih.gov/pubmed/35890406 http://dx.doi.org/10.3390/pharmaceutics14071511 |
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author | Lee, Yue-Zhi Hsu, Hsing-Yu Yang, Cheng-Wei Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju |
author_facet | Lee, Yue-Zhi Hsu, Hsing-Yu Yang, Cheng-Wei Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju |
author_sort | Lee, Yue-Zhi |
collection | PubMed |
description | Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm. |
format | Online Article Text |
id | pubmed-9325102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93251022022-07-27 The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b Lee, Yue-Zhi Hsu, Hsing-Yu Yang, Cheng-Wei Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju Pharmaceutics Article Ciclesonide is an inhaled corticosteroid used to treat asthma and has been repurposed as a treatment for mildly ill COVID-19 patients, but its precise mechanism of action is unclear. Herein, we report that ciclesonide blocks the coronavirus-induced production of the cytokines IL-6, IL-8, and MCP-1 by increasing IκBα protein levels and significantly decreasing p65 nuclear translocation. Furthermore, we found that the combination of ciclesonide and dbq33b, a potent tylophorine-based coronavirus inhibitor that affects coronavirus-induced NF-κB activation a little, additively and synergistically decreased coronavirus-induced IL-6, IL-8, and MCP-1 cytokine levels, and synergistically inhibited the replication of both HCoV-OC43 and SARS-CoV-2. Collectively, the combination of ciclesonide and dbq33b merits consideration as a treatment for COVID-19 patients who may otherwise be overwhelmed by high viral loads and an NF-κB-mediated cytokine storm. MDPI 2022-07-21 /pmc/articles/PMC9325102/ /pubmed/35890406 http://dx.doi.org/10.3390/pharmaceutics14071511 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Yue-Zhi Hsu, Hsing-Yu Yang, Cheng-Wei Lin, Yi-Ling Chang, Sui-Yuan Yang, Ruey-Bing Liang, Jian-Jong Chao, Tai-Ling Liao, Chun-Che Kao, Han-Chieh Chang, Jang-Yang Sytwu, Huey-Kang Chen, Chiung-Tong Lee, Shiow-Ju The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title | The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title_full | The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title_fullStr | The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title_full_unstemmed | The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title_short | The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b |
title_sort | synergistic inhibition of coronavirus replication and induced cytokine production by ciclesonide and the tylophorine-based compound dbq33b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325102/ https://www.ncbi.nlm.nih.gov/pubmed/35890406 http://dx.doi.org/10.3390/pharmaceutics14071511 |
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